The over-arching goal of the Program Project is to build bridges across disciplines: to link higher cognitive functions, their underlying neurobiological bases, and their molecular genetic underpinnings, using Williams functional magnetic resonance imaging with molecular genetics to study each individual. WMS is a rare genetically based disorder that generally results in mental retardation, distinctive faces, and a specific heart defect. Studies so far suggest that the syndrome also results in a characteristic cognitive profile of dissociations both within and across cognitive domains: severe intellectual deficits but relatively spared language; and severe deficits in spatial construction, but remarkable preserved face processing. These dissociations in higher cognitive functioning make WMS an invaluable paradigm for the study of brain- behavior relationships, and for the mapping of brain and behavior phenotypes to the genome. Subproject 0001 WMS, investigating consistency, variability and the bases for dissociations. Subproject 0002 (Neurophysiological Characterization) will investigate the neural correlates of this cognitive profile, using electrophysiological resolution structural and functional magnetic resonance imaging to investigate neural systems in WMS; Subproject 0004 (Cellular and Molecular Architectonics) will address histological changes in neuronal architecture and gene expression in WMS, and Subproject 0005 (The Molecular Genetic Characterization of Williams Syndrome) will seek an understanding of the molecular genetic basis of the disorder. These Diagnostic Methods and Services. Through links across subprojects 0001, 0002, 0003, 0004, 0004 we will begin to define pathways between genotype and cognitive as well as neural phenotype of WMS. Studies of this unusual disorder, Williams syndrome, will provide new opportunities to explore fundamental issues of cognitive neuroscience that relative cognitive functions to brain organization and to their genetic bases.